Genomic landscape of neutrophilic leukemias of ambiguous diagnosis.

Zhang H, Wilmot B, Bottomly D, Dao KT, Stevens E, Eide CA, Khanna V, Rofelty A, Savage S, Reister Schultz A, Long N, White L, Carlos A, Henson R, Lin C, Searles R, Collins RH, DeAngelo DJ, Deininger MW, Dunn T, Hein T, Luskin MR, Medeiros BC, Oh ST, Pollyea DA, Steensma DP, Stone RM, Druker BJ, McWeeney SK, Maxson JE, Gotlib JR, Tyner JW.

Blood

September 12, 2019

Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities.

Program:
CTD²
Last updated: June 28, 2020